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6 Things to Know About Neutropenic Fever in the Oncology Patient

1. Neutropenic Fever (NF) is defined as a single oral or axillary temperature of > 38.3°C (101°F) or a temperature > 38.0°C (100.4°F) sustained over 60 minutes in a patient with an absolute neutrophil count < 500/µL (1).

2. It is actually uncommon for a definite etiology to be determined for an episode of NF. Only 20-35% of episodes of NF are due to a clinically documented infection. This should be expected since NF may be due to the underlying malignancy itself (e.g., leukemia), mucositis, toxicity of the chemotherapeutic agents, or a host of other etiologies (1-3).

3. A neutropenic patient will not be able to mount a robust inflammatory response, and thus the sensitivity of a CXR will decrease (1).

4. Broad-spectrum antibiotics should be administered within 60 minutes once NF is identified and appropriate cultures have been obtained (1).

5. Empiric coverage for gram-positive organisms (e.g., vancomycin) is indicated in patients who are hypotensive, have a skin and soft tissue source, are currently taking a fluoroquinolone or TMP-SMX, or who have an indwelling line (1,4).

6. It is no longer standard to admit all NF patients to the hospital. Select patients (i.e., not septic, no major co-morbid illness, stable social situation) may be suitable for outpatient management. Most experts recommend using the Multinational Association for Supportive Care in Cancer score for assistance with disposition decisions (1,5).

TAKE HOME POINTS: USE SCORING SYSTEM TO DISPO LOW RISK NEUTROPENIC FEVER

MASCC Risk Index Score (mascc.org)

CISNE Score (CISNE Score)

Source: EMedHome, RebelEM

Why CARE!? Such a high FALSE POSITIVE rate for subsegmental PEs on CTA is 60%!!! Studies with multiple blinded radiology reads. Segmental FALSE positives = 25%.

Not a benign evaluation: Contrast risk of infiltration or anaphylactoid reaction. Malignancy risk from radiation is 1/100 for women and 1/500. Increased risk of repeat CT imaging in the future 7x!!

PE: 1/400 or 1/1500 incidence of PE total for ED presentations in US

Mortality: 8% (30 day mortality after PE diagnosis). On autopsy up to 30% found to have PE (unknown other cause of death)

Vital Signs:

SpO2: <95% (94 and below)

HR: >100 at ANY time per guidelines

RR: No recognized agreement (triage RR often blanket value – 20 for all. Some say 20 vs 24, etc.)

Temp: >102.5 F, less likely to be PE (wash between 100.4 and 102.5)

Risk Factors:

Prior VTE (PE/DVT): Unprovoked vs. provoked. Unprovoked is more concerning, even with normal coagulopathy panel

Malignancy History: Definition of active cancer – metastatic disease state and/or active treatment within 6 months. High risk – pancreatic, Multiple myeloma, colon, glioblastoma, melanoma. Some chemo treatments more risk inducing (eg. ALL chemo)

Immobility: Casting, trauma patients in particular, no necessarily hospitalization. 6 hours of continuous seated position. Surgery: with intubation/general anesthesia and/or epidural. Knee, abdominal, neurological.

OCPs: estrogen of any form. Not really men.

Pregnancy: postpartum, way increased risk. Symptomatic patients = 70% risk.

Increased risk at age 50: Perpetually increases with age.

Symptoms:

Pleuritic chest pain: suggest peripheral PEs (65%)

Hemoptysis: hemorrhage, not infarct

Exertional Dyspnea: Subacute = 3-7ish days, insidious increase (often do not reports CP, usually central clot). vs. Acute

Calf pain/Calf swelling: symptom and PE finding

Syncope: large clot burden

Anticoagulation: Compliance = less likely. NOACs, if compliant, they are therapeutic. Coumadin, variable levels

Not significant: orthopnea, palpitations, anxiety, dizziness

Physical Exam Findings:

Abnormal pulmonary exam – decreases likelihood

Calf edema – increases likelihood

STEP 1: Do you, based on the information above, feel that a PE is possible? Meaning, it is ABOVE the 2% threshold for PE. (if you have less than a 2% clinical suspicion for PE, STOP. You do NOT think there is a PE and you do not evaluate further. I repeat – STOP! Evaluate for other suspected pathologies).

ACEP Guidelines: 2% is an acceptable cutoff recognizing limitations of testing and risk of false positives

So nowwwwww, clinically feel that PE is possible.

STEP 2: RISK STRATIFY

Wells Score vs. Geneva vs. Gestalt: all relatively equivalent

These are NOT used to rule out. They are only to RISK STRATIFY, meaning that you clinically have a suspicion of said disease so then you risk stratify.

Low – Moderate – High

STEP 3: Based on risk, apply appropriate next evaluation steps (imaging, lab test, or clinical decision tool)

High: Wells, Geneva, Gestalt High -> CTA. Can consider empiric heparin pre CTA or post.

Moderate: D-dimer. Value cutoff chosen to have <2% of PE. Yes, do age adjusted cutoffs. Look at the units (Hx10 fibrinogen unit. Ddimer unit Hx5). Starts at age 50 and above. (NOT a screen for people who you think do not have a PE. You have a clinical concern for PE, they are moderate or low risk).

Low: PERC – only patient population because the inclusion criteria is only low risk for PE. If PERC+, then you d-dimer.

If limited CTA with inadequate imaging obtained and VSS, expert recommendation is to obtain a ddimer if not done so. If negative, discharge. If ddimer positive, obtain LE ultrasounds. If no DVT, discharge +/- anticoagulation for PE based on actual risk factors and follow up. (Look at age/real risk factors/trop/BNP/echo/PESI score).

Disposition:

Stable vs. Unstable.

Unstable: hypotensive -> tPa and MICU

Stable: BNP/trop/echo R heart strain -> heparin +/- half dose tPa and admit to ICU/tele

If normal BNP/trop/echo -> PESI Score -> HIGH gets heparin to floor. Low PESI give lovenox shots and discharge (no evidence/FDA approval for NOACs).

Subsegmental PEs: ACEP – No risk factors for recurrence, no DVT on b/l US -> can be sent home on no AC and refer to PCP for PE surveillance for symptoms of PE.

Young and VSS with subsegmental PE: really low risk for negative outcome for PE